International Journal of Biological Macromolecules最新文献

{"title":"Targeting the phosphoprotein enriched in diabetes/astrocytes 15 death effector domain via fragment-based and integrative structural biology approaches.","authors":"Ivan Mercurio, Federica Carucci, Vittoria Nanna, Sara Di Marino, Maria Giovanna Eva Papadopoulos, Martina Bischetti, Francesca Fata, Gaetano Malgieri, Dritan Siliqi, Alessandro Piai, Roberto Fattorusso, Giuseppe Felice Mangiatordi, Carlo Toniatti, Michele Saviano, Domenico Alberga","doi":"10.1016/j.ijbiomac.2026.154849","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154849","url":null,"abstract":"<p><p>Phosphoprotein Enriched in Diabetes/Astrocytes 15 (PED/PEA-15) is a 15 kDa adaptor protein whose overexpression drives tumorigenesis and type II diabetes through dysregulated protein-protein interactions (PPIs) mediated by its Death Effector Domain (DED). Despite its therapeutic relevance, no potent small-molecule inhibitors targeting the DED have yet been identified. Here, we employed a fragment-based drug discovery approach combining ¹⁹F and ¹H NMR screening of a 118-compound fluorinated library to identify F2 a fragment that binds the PED/PEA-15 DED with an estimated dissociation constant of 150 μM. NMR chemical shift perturbation analysis mapped the binding site to the α2-α3 loop, α3, and α5 helices. To better characterise the protein, Small-angle X-ray scattering of the apo protein was employed, yielding a structural model in which the C-terminal tail is consistent with a conformation that is not maximally extended. Induced fit docking and molecular dynamics simulations of the PED/PEA-15-F2 complex supported a plausible binding pose and suggested a ligand-induced destabilisation of the α3 helix propagating to the α6 helix. Correlation network analysis further suggests a hypothesis in which F2 rewires the dynamic architecture of the DED and alters allosteric communication between residues of the DED and the C-terminal tail. The identification of a ligand-accessible site on the DED supports the druggability of PED/PEA-15 and provides a refined structural framework for fragment optimisation and for testing whether engagement of this site can be translated into modulation of PED/PEA-15 PPIs with therapeutic potential in cancer and type II diabetes.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154849"},"PeriodicalIF":8.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Development of a sustainable antimicrobial biopolymer film for preventing post-harvest food spoilage\" [Int. J. Biol. Macromol. 374 (2026) /153247].","authors":"Shubhi Joshi, Aastha Arora, Mayank Maan, Ikshika Sharely, Umang Mudgil, Panchali Barman, Rishu, Ravneet Kaur, Avneet Saini","doi":"10.1016/j.ijbiomac.2026.154857","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154857","url":null,"abstract":"","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154857"},"PeriodicalIF":8.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Context-dependent immunomodulation by Astragalus polysaccharides: Structural determinants, structure-activity relationships, mechanisms, and applications: A review.","authors":"Mengyuan Wang, Yuan Li, Hongliang Xu, Bo Xu, Xiaorui Qu, Jiayan Zhao, Dongfeng Yang, Zongsuo Liang","doi":"10.1016/j.ijbiomac.2026.154888","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154888","url":null,"abstract":"<p><p>Astragalus polysaccharides (APS), derived mainly from Astragalus membranaceus (Fisch.) Bunge and Astragalus membranaceus var. mongholicus (Bunge) P. K. Hsiao, have attracted considerable attention as plant-derived immunomodulatory macromolecules. Accumulating evidence suggests that APS-mediated immunomodulation is context-dependent rather than unidirectional. Raw-material characteristics, processing methods, extraction procedures, fractionation, and purification can generate APS fractions with different structural characteristics, including molecular weight distribution, monosaccharide composition, glycosidic linkages, branching patterns, chain conformation, solubility, and aggregation behavior. This review summarizes recent progress in APS structural characterization, structure-activity relationships, immunomodulatory effects, mechanisms of action, and immune-related applications. Under immunosuppressive conditions, APS may help restore impaired immune defenses, whereas during immune hyperactivation, APS may suppress excessive inflammatory responses and support immune homeostasis. Mechanistically, APS may modulate innate and adaptive immune responses, gut microbial composition and metabolite production, mucosal barrier function, and gut-organ communication. Toll-like receptor 4-associated nuclear factor-κB and mitogen-activated protein kinase pathways are among the most frequently reported mechanisms, whereas nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling, regulation of the NOD-like receptor family pyrin domain-containing 3 inflammasome, interleukin-22/signal transducer and activator of transcription 3 signaling, and microbiota-mediated pathways may contribute in specific settings. In addition, APS-based interventions have been investigated for supportive clinical care, vaccine adjuvants, veterinary use, functional foods, immune-support products, and pharmaceutical or topical formulations. By linking structural variation to immune effects, mechanistic pathways, and application contexts, this review provides a basis for the structural standardization of APS, quality control, activity optimization, and immune-related product development.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154888"},"PeriodicalIF":8.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological targeting of FKBPL with rapamycin sensitizes triple-negative breast cancer to ferroptosis.","authors":"Rongxue Li, Hang Ke, Zihan Chen, Jiatian Xu, Da Qian, Bo Luo, Shirin Jamshidi, Zhengguo Zhang, Hong'en Xu, Jing Sun, Hanchu Xiong","doi":"10.1016/j.ijbiomac.2026.154874","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154874","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) remains a clinically formidable subtype, while resistant to conventional apoptotic cell death pathways, it exhibits a unique and exploitable vulnerability to ferroptosis. Here, we identify the FK506-binding protein-like (FKBPL) as a novel scaffold that dictates ferroptosis sensitivity and promotes TNBC progression. Bioinformatic and clinical analyses revealed that FKBPL was significantly overexpressed in TNBC and correlated with inferior patient prognosis. Functional characterization demonstrated that FKBPL knockdown markedly impaired TNBC cell proliferation and migration in vitro and suppressed tumor growth in vivo. Mechanistically, FKBPL modulated the kelch-like ECH associated protein 1 (KEAP1)-associated ubiquitination and increased nuclear factor erythroid-related factor 2 (NRF2) protein abundance, reinforcing cellular antioxidant defenses and reducing ferroptosis sensitivity. Notably, the clinically approved agent rapamycin was found to directly bind to FKBPL, inducing its proteasomal degradation and significantly sensitizing TNBC cells to ferroptosis. Given the emerging links between ferroptosis and immunogenicity, single-cell transcriptomic analysis further illustrated that FKBPL⁺ malignant cells are predicted to interact with neighboring immune compartments, suggesting a potential association with microenvironmental remodeling within the TNBC microenvironment. Collectively, this study identifies FKBPL as a pivotal regulatory node connecting protein homeostasis with ferroptosis and provides a mechanistic rationale for repurposing rapamycin to therapeutically target the inherent ferroptotic vulnerability of TNBC.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154874"},"PeriodicalIF":8.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction between FmRAV4 (a RAV transcription factor) and FmMYB1 (a MYB transcription factor) confers drought tolerance via ROS scavenging in Fraxinus mandshurica.","authors":"Xianguang Nie, Xianhui Nie, Xuefei Xu, Yueliang Wu, Tongyao Bai, Xueting Ma, Zizhuo Zhao, Ai Zheng, Xiaoman Cui, Jiani Xie, Xiaoyu Ji","doi":"10.1016/j.ijbiomac.2026.154851","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154851","url":null,"abstract":"<p><p>Drought stress severely restricts plant growth and development. Although AP2/ERF family transcription factors (TFs) participate extensively in abiotic stress responses, they remain largely unexplored in Fraxinus mandshurica. In this study, we identified and functionally characterized FmRAV4, a TF from the RAV subfamily. FmRAV4 is localized in the nucleus, lacks transcriptional activation activity, and is significantly upregulated in leaves under drought stress. Functional analyses using transient overexpression, gene silencing in F. mandshurica, and stable transformation in Arabidopsis thaliana demonstrated that FmRAV4 enhances drought tolerance by increasing SOD and POD activities, scavenging excessive reactive oxygen species (ROS), and alleviating membrane lipid peroxidation. Mechanistically, yeast one-hybrid, EMSA, and ChIP-qPCR assays revealed that FmRAV4 directly binds to conserved CAACA motifs in the promoters of FmSOD2, FmPOD1, FmPOD2, and FmPOD4 to activate their transcription. Importantly, yeast two-hybrid, luciferase complementation imaging, and pull-down assays confirmed that FmRAV4 physically interacts with FmMYB1 both in vivo and in vitro, and that FmMYB1 upregulation improves drought tolerance in F. mandshurica. Co-overexpression of these two genes synergistically activates antioxidant genes in a concentration-dependent manner, thereby enhancing ROS scavenging and conferring stronger drought tolerance than single-gene overexpression. Collectively, these findings reveal that the FmRAV4-FmMYB1 interaction forms a synergistic regulatory module mediating drought tolerance, providing valuable genetic resources for the molecular breeding of drought-tolerant woody plants.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154851"},"PeriodicalIF":8.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Construction of protein-polysaccharide complexes: Category, organoleptic impaction and application in the food industry\" [Int. J. Biol. Macromol. Volume 321, Part 3, 2025, 146422, ISSN 0141-8130].","authors":"Ning Li, Juan Huang, Chen Chen, Haiyan Yu, Huaixiang Tian","doi":"10.1016/j.ijbiomac.2026.154854","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154854","url":null,"abstract":"","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154854"},"PeriodicalIF":8.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic lignin-quercetin nano-architectures: Rational design of bio-based systems for multifunctional cosmetics.","authors":"M Rodríguez-Aranda, M Peña-Ortiz, L Serrano","doi":"10.1016/j.ijbiomac.2026.154853","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154853","url":null,"abstract":"<p><p>Developing sustainable, high-performance cosmetic formulations requires a paradigm shift toward multifunctional ingredients that combine efficacy with environmental responsibility. In this work, sustainable cream formulations were rationally designed through the synergistic integration of lignin and quercetin, employing a controlled solvent-exchange precipitation approach optimized via ζ-potential analysis and systematic selection of technical lignins. The resulting lignin-quercetin hybrid system were incorporated into topical formulations and evaluated for their photoprotective, antioxidant and antimicrobial performance. The developed systems exhibited outstanding broad-spectrum ultraviolet (UV) shielding, achieving transmittance profiles comparable to commercial Sun Protection Factor (SPF) 30 formulations, while also promoting safer energy dissipation pathways. In addition, a pronounced synergistic antioxidant effect was observed, preserving the high radical-scavenging activity achieved with 7 wt% free quercetin using only 1.4 wt% quercetin incorporated into the lignin-quercetin hybrid (80% reduction in quercetin content). Furthermore, some formulations showed antimicrobial activity against representative human pathogenic microorganisms with distinct cell wall features and exhibited a cellular viability above 70% in concentrations up to 100 μg·mL^-1 . Overall, these findings establish a robust platform for the development of lignin-based hybrid systems, positioning them as promising candidates for next-generation sustainable cosmetic applications.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154853"},"PeriodicalIF":8.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultraviolet-crosslinked nerve growth factor-β hydrogel promotes cavernous nerve regeneration and functional recovery in neurogenic erectile dysfunction.","authors":"Chao Luo, Yaqian Peng, Xiongcai Zhou, Junlin Tian, Mengni Zhu, Bo Wang, Xiaolan Qi, Tao Qi","doi":"10.1016/j.ijbiomac.2026.154886","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154886","url":null,"abstract":"<p><p>Neurogenic erectile dysfunction (ED) caused by cavernous nerve injury remains difficult to treat because conventional therapies improve erectile responses without repairing the underlying neurovascular damage. Here, a photocrosslinkable hydrogel composed of gelatin methacryloyl (GelMA) and hyaluronic acid methacrylate (HAMA) was developed for localized and sustained delivery of nerve growth factor-β (NGF-β). The GelMA/HAMA precursor exhibited shear-thinning behavior and underwent rapid ultraviolet-induced gelation, while the resulting hydrogel showed gradual degradation and sustained NGF-β release. After ultraviolet exposure, 88.37-99.77% of NGF-β remained detectable by enzyme-linked immunosorbent assay across the tested assay concentrations, and release samples collected through day 7 retained neurite-promoting activity in PC-12 cells. In mouse Schwann cells, the NGF-β-loaded hydrogel enhanced proliferation and activated AKT- and ERK-associated signaling. In rats with bilateral cavernous nerve crush injury, local treatment increased the maximal intracavernous pressure/mean arterial pressure ratio, improved cavernous tissue architecture, enhanced neurovascular and myelin-associated markers, and improved reproductive outcomes. The most pronounced functional recovery was observed after in situ photocrosslinking of the NGF-β-loaded hydrogel. These findings establish a localized neuroregenerative platform that couples light-triggered hydrogel formation with sustained NGF-β delivery for cavernous nerve injury-induced ED.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154886"},"PeriodicalIF":8.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ethyl cellulose-alginate/poly(vinyl alcohol) dual-layer coating incorporating biochar-immobilized PGPR for controlled urea release, water retention, and plant stress resilience.","authors":"Siqi Guo, Xiaoyan Qian, Shengnan Zhang, Desheng Wang, Mukkram Ali Tahir, Chong Liu, Fayong Li","doi":"10.1016/j.ijbiomac.2026.154873","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154873","url":null,"abstract":"<p><p>Coated controlled-release fertilizers can synchronize nutrient supply with crop demand, yet single-layer systems are often limited by poor structural integrity and restricted functionality. Here, salt-tolerant plant growth-promoting rhizobacteria (PGPR) were immobilized on biochar and embedded in a dually crosslinked poly(vinyl alcohol)/sodium alginate hydrogel (PSBP). A dual-layer controlled-release urea fertilizer (PSBPEU-CRF) was fabricated using an ethyl cellulose inner diffusion barrier and a PSBP outer hydrogel coating. PSBPEU-CRF enabled sustained viable-cell release and improved bacterial immobilization stability. PSBP hydrogel reached an equilibrium swelling ratio of 424%, improved soil water retention and showed 70.65% mass loss after 28 d. At 2% (w/w), soil water retention remained 20.96% on day 10, compared with 2.35% in unamended soil. PSBPEU-CRF markedly retarded urea release in water and soil; the release profiles fitted the Korsmeyer-Peppas model, indicating anomalous transport governed by diffusion and polymer-network swelling/relaxation. In saline-alkali pakchoi pots, PSBPEU-CRF increased chlorophyll accumulation and antioxidant enzyme activities while reducing lipid peroxidation and the Na⁺/K⁺ ratio. Overall, the integration of controlled nutrient release, soil water retention, and rhizosphere functional regulation provided by the PSBP hydrogel layer offers a promising approach for developing multifunctional fertilizers for salt-affected soils. Nevertheless, its long-term field performance, manufacturing scalability, and economic feasibility require further evaluation.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154873"},"PeriodicalIF":8.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a CREB-regulated transcription coactivator (CRTC) in Crassostrea gigas and its role in regulating melanin production.","authors":"Jinhai Zhang, Nan Gao, Xuexin Yu, Wenhao Yang, Yulu Jiang, Chen Liu, Yijing Han, Yaqiong Liu, Xiaotong Wang","doi":"10.1016/j.ijbiomac.2026.154875","DOIUrl":"10.1016/j.ijbiomac.2026.154875","url":null,"abstract":"<p><p>Shell pigmentation is a critical economic trait that influences the commercial value of aquacultural oyster, with coloration primarily governed by melanin deposition. In melanin biosynthesis, the cAMP-CREB-MITF signaling axis serves as the core regulatory pathway, wherein the CREB-regulated transcription coactivator (CRTC) functions as an important coactivator for CREB. In this study, we identified and functionally characterized the CRTC homologous gene CgCRTC from the Pacific oyster (Crassostrea gigas). The CgCRTC gene encodes a 669-amino-acid protein with three conserved functional domains: an N-terminal CREB-binding domain (CBD), a central regulatory domain (REG), and a C-terminal trans-activating domain (TAD). Phylogenetic analysis confirmed its close evolutionary grouping with other molluscan orthologs. While CgCRTC transcripts were ubiquitously detected across all examined tissues, expression levels peaked in the gill and smooth adductor muscle. Subcellular localization revealed that the CgCRTC protein is predominantly cytoplasmic. RNAi-mediated silencing of CgCRTC led to a significant transcriptional downregulation of key melanogenic genes CgMITF, CgTYR and CgOCA2 in oysters. Furthermore, dual-luciferase assays demonstrated that CgCRTC activates the promoters of CgMITF, CgTYR and CgOCA2, and overexpression of CgCRTC in mouse B16F10 melanoma cells leads to an increase in melanin deposition. Collectively, our findings demonstrate that CgCRTC acts as a positive regulator of melanogenesis by transcriptionally upregulating the expression of CgMITF, CgTYR and CgOCA2.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154875"},"PeriodicalIF":8.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}